Aging, HIV

[Guest guest]

Aging, HIVfrom Jules: In light of the unexpected on my part of the controversy around this recent one VA study I've collected below only some of the many studies published & presented at conferences over the past 2 years, read for yourself. The first link is to the MACS Study finding of increased frailty in HIV+ individuals.HIV-1

Infection Is Associated With an Earlier Occurrence of a Phenotype Related to Frailty: HIV+ men in MACS 10-Times More Likely to Exhibit Frailty than HIV-negative Men. - (04/20/09)"The estimated prevalence of the FRP(frailty) for 55-year-old white non-Hispanic, college-educated men HIV-infected for ≦ 4

years was 3.4% equivalent to the estimate for uninfected men of the same ethnicity and education at age 65 years or older.".....from Jules: in table 4 below for patients without AIDS risk for frailty was 2.42 if one had HIV for <4

years but 6.25 if one had HIV for 8-12 years suggesting that frailty risk increased 3 fold after having HIV for 10 years, further suggesting the unfathomable increased risk for frailty after having HIV for 20-30 years!!!.....In figure 2a below the prevalence of frailty was 13.4% for HIV+ persons 55 years of age with HIV for 8-12 years of duration!!!! where AIDS conditions may be an issue but 5.8% where AIDS conditions may

not be an issue.CROI:

Immune Senescence, Activation, and Abnormal T Cell Homeostasis despite Effective HAART, a Hallmark of Early Aging in HIV Disease: "HIV-infected

subjects (median 56 years) with good immune reconstitution and viral suppression had immune changes comparable to older (median 88 years) HIV-negative subjects" - (02/20/09)CROI: HIV Infection May Make the Brain 15 to 20 Years Older:

HIV slows cerebral blood flow and stimulus response in MRI study - written by Mark Mascolini - (02/23/09)"There is about a 15-year brain aging because of HIV-infection"Causes of Accelerated Aging in HIV: HIV Induces Aging of T-Cells - (02/10/09)"HIV-1 infection induces premature aging of both memory T cells and naive CD4+ T cells; in particular, the fast progressors (FPs) experience accelerated aging of lymphocytesEarly Immune Senescence in HIV Disease - (02/15/10)Activation and inflammation due to persistent infection such as HIV also provide a milieu for accelerated replicative senescence of T cells that progressively accumulate during the normal course of aging.....The proof of this concept comes from data

from the Strategies for Management of Antiretroviral Therapy (SMART) study, which shows elevated levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 to be associated with non-AIDS-defining

co-morbidities in HAART-suppressed patients.increased levels of these biomarkers were

associated with both all-cause mortality and cardiovascular disease events in HIV-infected participants.Inflammation and Complications of HIV Disease - EDITORIAL COMMENTARY - (05/07/10)Pre-HAART Immune Activation Associated with Developing Cancers & Death - (05/07/10)Coronary Aging in HIV-Infected Patients - (09/23/10)"....these data suggest that accelerated vascular aging is common among HIV-infected persons. To reduce the impact of cardiovascular disease in this population, additional data on the pathogenesis of increasing vascular age-and ultimately therapeutic strategies to slow aging-are needed.Coronary

Aging in HIV-Infected Patients: "Increased vascular age was observed in

162 patients (40.5%), with an average increase of 15 years"...."you are

50 years old but your heart's age is 65" - pdf attached - (09/23/10)Inflammation Predicts Mortality in FRAM - (07/08/10)Our findings that fibrinogen and CRP (inflammation markers) remained associated with higher odds of death regardless of the degree of immunosuppression (200 cd4 vs >500 cd4) suggests that inflammation

remains an important factor even in those with relatively preserved CD4 cells......high CRP (>3 mg/L) was associated with a 3.7-fold higher odds of death compared to those with low CRP (<1 mg/L) (Table 2).....After further adjustment for markers of renal disease (ie, microalbuminuria and eGFR based on cystatin C), fibrinogen and CRP remained associated with higher odds of overall death and death in every

CD4 category (data not shown)."Mitochondria provide a potential link between internal and external triggers of the innate immune responseImmunology & Mitochondria - Clinical immunology: Culprits with evolutionary ties - (06/07/10)Immunosenescence & Aging in HIV - (10/22/10)The early occurrence of T cell senescence (immune senescence) and correlation to activation and inflammation is established.Seema Desai, PhDAnd there is clear evidence of bone loss reports in HIV-infected persons before the era of ART, so bone changes cannot be blamed on the medications,, but rather, may actually relate to T cell-mediated inflammation. In studies that are unrelated to HIV/AIDS, it has been shown that senescent T cells accumulate in many forms of cancer, putatively due to chronic stimulation with tumor antigens. Thus, many pathologies normally seen in older individuals are accelerated in HIV disease, and may ultimately relate to T cell senescence, as Seema has written.Rita Effros, PhDSystemic inflammation, from any cause, accelerates chronic disease processes.In HIV, one system clearly recapitulates time-dependent degradation: the immune system. We consider two aspects of that: increased innate activity (inflammation) and decreased adaptive

activity (immunosenescence). The elderly slowly but surely have increased inflammation, and slowly but surely become immunosenescent.But you DO have a rapid buildup of inflammation

in HIV, and a rapid immunosenescence none the less. We believe that a pro-inflammatory melieu accelerates the pathophysiology in most chronic diseases, so one would anticipate seeing earlier incidence of clinical diagnoses such as coronary heart disease, T2DM, dementia, COPD, CKD, all

of which are associated with older age if the inflammation isn't present (unless a person has a powerfully predisposing genetic or environmental issue at play) , PhDThere appears to be many contributing factors including accelerated immune senescence and many others including viral reservoirs, concomittant chronic diseases, poor diet/exercise/unhealthy lifestyle etc. In the meantime we don't have much time to lose, many HIV+ individuals are over 50 and over 60 already and do not have time to

wait for study results that take many years. They need interventions and a better understanding of what is going on. So we need to try and find a way to reverse senescence.Jules Levin, NATAP